Cost-Effectiveness Analysis of Four Simulated Colorectal Cancer Screening Interventions, North Carolina

Colorectal cancer (CRC) screening rates are suboptimal, particularly among the uninsured and the under-insured and among rural and African American populations. Little guidance is available for state-level decision makers to use to prioritize investment in evidence-based interventions to improve their population’s health. The objective of this study was to demonstrate use of a simulation model that incorporates synthetic census data and claims-based statistical models to project screening behavior in North Carolina

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

The LIGO HET Response (LIGHETR) Project to Discover and Spectroscopically Follow Optical Transients Associated with Neutron Star Mergers

The LIGO HET Response (LIGHETR) project is an enterprise to follow up optical transients (OT) discovered as gravitational wave merger sources by the LIGO/Virgo collaboration (LVC). Early spectroscopy has the potential to constrain crucial parameters such as the aspect angle. The LIGHETR collaboration also includes the capacity to model the spectroscopic evolution of mergers to facilitate a real-time direct comparison of models with our data. The principal facility is the Hobby-Eberly Telescope. LIGHETR uses the massively-replicated VIRUS array of spectrographs to search for associated OTs and obtain early blue spectra and in a complementary role, the low-resolution LRS-2 spectrograph is used to obtain spectra of viable candidates as well as a densely-sampled series of spectra of true counterparts. Once an OT is identified, the anticipated cadence of spectra would match or considerably exceed anything achieved for GW170817 = AT2017gfo for which there were no spectra in the first 12 hours and thereafter only roughly once daily. We describe special HET-specific software written to facilitate the program and attempts to determine the flux limits to undetected sources. We also describe our campaign to follow up OT candidates during the third observational campaign of the LIGO and Virgo Scientific Collaborations. We obtained VIRUS spectroscopy of candidate galaxy hosts for 5 LVC gravitational wave events and LRS-2 spectra of one candidate for the OT associated with S190901ap. We identified that candidate, ZTF19abvionh = AT2019pip, as a possible Wolf-Rayet star in an otherwise unrecognized nearby dwarf galaxy.Comment: 26 pages, 15 figure

Climate and lawn management interact to control C4 plant distribution in residential lawns across seven U.S. cities.

Author Posting. © Ecological Society of America, 2019. This article is posted here by permission of Ecological Society of America for personal use, not for redistribution. The definitive version was published in Trammell, T. L. E., Pataki, D. E., Still, C. J., Ehleringer, J. R., Avolio, M. L., Bettez, N., Cavender-Bares, J., Groffman, P. M., Grove, M., Hall, S. J., Heffernan, J., Hobbie, S. E., Larson, K. L., Morse, J. L., Neill, C., Nelson, K. C., O'Neil-Dunne, J., Pearse, W. D., Chowdhury, R. R., Steele, M., & Wheeler, M. M. Climate and lawn management interact to control C4 plant distribution in residential lawns across seven U.S. cities. Ecological Applications, 29(4), (2019): e01884, doi: 10.1002/eap.1884.In natural grasslands, C4 plant dominance increases with growing season temperatures and reflects distinct differences in plant growth rates and water use efficiencies of C3 vs. C4 photosynthetic pathways. However, in lawns, management decisions influence interactions between planted turfgrass and weed species, leading to some uncertainty about the degree of human vs. climatic controls on lawn species distributions. We measured herbaceous plant carbon isotope ratios (δ13C, index of C3/C4 relative abundance) and C4 cover in residential lawns across seven U.S. cities to determine how climate, lawn plant management, or interactions between climate and plant management influenced C4 lawn cover. We also calculated theoretical C4 carbon gain predicted by a plant physiological model as an index of expected C4 cover due to growing season climatic conditions in each city. Contrary to theoretical predictions, plant δ13C and C4 cover in urban lawns were more strongly related to mean annual temperature than to growing season temperature. Wintertime temperatures influenced the distribution of C4 lawn turf plants, contrary to natural ecosystems where growing season temperatures primarily drive C4 distributions. C4 cover in lawns was greatest in the three warmest cities, due to an interaction between climate and homeowner plant management (e.g., planting C4 turf species) in these cities. The proportion of C4 lawn species was similar to the proportion of C4 species in the regional grass flora. However, the majority of C4 species were nonnative turf grasses, and not of regional origin. While temperature was a strong control on lawn species composition across the United States, cities differed as to whether these patterns were driven by cultivated lawn grasses vs. weedy species. In some cities, biotic interactions with weedy plants appeared to dominate, while in other cities, C4 plants were predominantly imported and cultivated. Elevated CO2 and temperature in cities can influence C3/C4 competitive outcomes; however, this study provides evidence that climate and plant management dynamics influence biogeography and ecology of C3/C4 plants in lawns. Their differing water and nutrient use efficiency may have substantial impacts on carbon, water, energy, and nutrient budgets across cities.This research was funded by a series of collaborative grants from the U.S. National Science Foundation Macrosystems Biology Program (EF‐1065548, 1065737, 1065740, 1065741, 1065772, 1065785, 1065831, 121238320). The authors thank La'Shaye Ervin, William Borrowman, Moumita Kundu, and Barbara Uhl for field and laboratory assistance

Continental-scale homogenization of residential lawn plant communities

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Landscape and Urban Planning 165 (2017): 54-63, doi:10.1016/j.landurbplan.2017.05.004.Residential lawns are highly managed ecosystems that occur in urbanized landscapes across the United States. Because they are ubiquitous, lawns are good systems in which to study the potential homogenizing effects of urban land use and management together with the continental-scale effects of climate on ecosystem structure and functioning. We hypothesized that similar homeowner preferences and management in residential areas across the United States would lead to low plant species diversity in lawns and relatively homogeneous vegetation across broad geographical regions. We also hypothesized that lawn plant species richness would increase with regional temperature and precipitation due to the presence of spontaneous, weedy vegetation, but would decrease with household income and fertilizer use. To test these predictions, we compared plant species composition and richness in residential lawns in seven U.S. metropolitan regions. We also compared species composition in lawns with understory vegetation in minimally-managed reference areas in each city. As expected, the composition of cultivated turfgrasses was more similar among lawns than among reference areas, but this pattern also held among spontaneous species. Plant species richness and diversity varied more among lawns than among reference areas, and more diverse lawns occurred in metropolitan areas with higher precipitation. Native forb diversity increased with precipitation and decreased with income, driving overall lawn diversity trends with these predictors as well. Our results showed that both management and regional climate shaped lawn species composition, but the overall homogeneity of species regardless of regional context strongly suggested that management was a more important driver.This research was supported by the Macrosystems Biology Program in the Emerging Frontiers Division of the Biological Sciences Directorate at the National Science Foundation (NSF) under grants EF-1065548, 1065737, 1065740, 1065741, 1065772, 1065785, 1065831, and 121238320

Climate and Lawn Management Interact to Control C\u3csub\u3e4\u3c/sub\u3e Plant Distribution in Residential Lawns Across Seven U.S. Cities

In natural grasslands, C4 plant dominance increases with growing season temperatures and reflects distinct differences in plant growth rates and water use efficiencies of C3 vs. C4 photosynthetic pathways. However, in lawns, management decisions influence interactions between planted turfgrass and weed species, leading to some uncertainty about the degree of human vs. climatic controls on lawn species distributions. We measured herbaceous plant carbon isotope ratios (δ13C, index of C3/C4 relative abundance) and C4 cover in residential lawns across seven U.S. cities to determine how climate, lawn plant management, or interactions between climate and plant management influenced C4 lawn cover. We also calculated theoretical C4carbon gain predicted by a plant physiological model as an index of expected C4 cover due to growing season climatic conditions in each city. Contrary to theoretical predictions, plant δ13C and C4 cover in urban lawns were more strongly related to mean annual temperature than to growing season temperature. Wintertime temperatures influenced the distribution of C4 lawn turf plants, contrary to natural ecosystems where growing season temperatures primarily drive C4 distributions. C4 cover in lawns was greatest in the three warmest cities, due to an interaction between climate and homeowner plant management (e.g., planting C4 turf species) in these cities. The proportion of C4 lawn species was similar to the proportion of C4 species in the regional grass flora. However, the majority of C4 species were nonnative turf grasses, and not of regional origin. While temperature was a strong control on lawn species composition across the United States, cities differed as to whether these patterns were driven by cultivated lawn grasses vs. weedy species. In some cities, biotic interactions with weedy plants appeared to dominate, while in other cities, C4 plants were predominantly imported and cultivated. Elevated CO2 and temperature in cities can influence C3/C4competitive outcomes; however, this study provides evidence that climate and plant management dynamics influence biogeography and ecology of C3/C4plants in lawns. Their differing water and nutrient use efficiency may have substantial impacts on carbon, water, energy, and nutrient budgets across cities

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN